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首页> 外文期刊>Synapse >Amphetamine and Environmentally Induced Hyperthermia Differentially Alter the Expression of Genes Regulating Vascular Tone and Angiogenesis in the Meninges and Associated Vasculature
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Amphetamine and Environmentally Induced Hyperthermia Differentially Alter the Expression of Genes Regulating Vascular Tone and Angiogenesis in the Meninges and Associated Vasculature

机译:苯丙胺和环境诱导的热疗差异性地改变了调节脑膜和相关脉管系统血管紧张度和血管生成的基因的表达。

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摘要

An amphetamine (AMPH) regimen that does not produce a prominent blood-brain barrier breakdown was shown to significantly alter the expression of genes regulating vascular tone, immune function, and angiogenesis in vasculature associated with arachnoid and pia membranes of the forebrain. Adult-male Sprague-Dawley rats were given either saline injections during environmentally-induced hyperthermia (EIH) or four doses of AMPH with 2 h between each dose (5, 7.5, 10, and 10 mg/kg d-AMPH, s.c.) that produced hyperthermia. Rats were sacrificed either 3 h or 1 day after dosing, and total RNA and protein was isolated from the meninges, arachnoid and pia membranes, and associated vasculature (MAV) that surround the forebrain. Vip, eNos, Drd1a, and Edn1 (genes regulating vascular tone) were increased by either EIH or AMPH to varying degrees in MAV, indicating that EIH and AMPH produce differential responses to enhance vasodilatation. AMPH, and EIH to a lesser extent, elicited a significant inflammatory response at 3 h as indicated by an increased MAV expression of cytokines Il1b, Il6, Ccl-2, Cxcl1, and Cxcl2. Also, genes related to heat shock/stress and disruption of vascular homeostasis such as Icam1 and Hsp72 were also observed. The increased expression of Ctgf and Timp1 and the decreased expression of Akt1, Anpep, and Mmp2 and Tek (genes involved in stimulating angiogenesis) from AMPH exposure suggest that angiogenesis was arrested or disrupted in MAV to a greater extent by AMPH compared to EIH. Alterations in vascular-related gene expression in the parietal cortex and striatum after AMPH were less in magnitude than in MAV, indicating less of a disruption of vascular homeostasis in these two regions. Changes in the levels of insulin-like growth factor binding proteins Igfbp1, 2, and 5 in MAV, compared to those in striatum and parietal cortex, imply an interaction between these regions to regulate the levels of insulin-like growth factor after AMPH damage. Thus, the vasculature and meninges surrounding the surface of the forebrain may be an important region in which AMPHs can disrupt vascular homeostasis. Synapse 63:881-894, 2009. Published 2009 Wiley-Liss, Inc.(dagger)
机译:苯丙胺(AMPH)方案不会产生明显的血脑屏障破坏,已显示可显着改变与前蛛网膜和pia膜相关的脉管系统中调节血管紧张,免疫功能和血管生成的基因的表达。成年雄性Sprague-Dawley大鼠在环境诱导的高温(EIH)期间进行了盐水注射,或者在两剂之间分别间隔2小时(5、7.5、10和10 mg / kg d-AMPH,sc)注射了四剂AMPH。产生高热。给药后3小时或1天处死大鼠,并从脑膜,蛛网膜和pia膜以及围绕前脑的相关脉管系统(MAV)分离总RNA和蛋白质。 EIH或AMPH可以在MAV中不同程度地增加Vip,eNos,Drd1a和Edn1(调节血管紧张度的基因),表明EIH和AMPH产生差异反应以增强血管舒张作用。如细胞因子Il1b,Il6,Ccl-2,Cxcl1和Cxcl2的MAV表达增加所指示的,AMPH和EIH在3小时内引起了明显的炎症反应。此外,还观察到了与热休克/应激和血管动态平衡破坏有关的基因,例如Icam1和Hsp72。从AMPH暴露中Ctgf和Timp1的表达增加,以及Akt1,Anpep和Mmp2和Tek(参与刺激血管生成的基因)的表达降低,表明AMPH与EIH相比,在MAV中血管生成被更大程度地阻止或破坏。 AMPH后,顶叶皮层和纹状体中与血管相关的基因表达的变化幅度小于MAV,表明在这两个区域中血管稳态的破坏较少。与纹状体和顶叶皮层中的胰岛素样生长因子结合蛋白Igfbp1、2和5的水平相比,纹状体和顶叶皮层中的水平发生变化,这意味着这些区域之间的相互作用调节了AMPH损伤后胰岛素样生长因子的水平。因此,围绕前脑表面的脉管系统和脑膜可能是AMPH可以破坏血管动态平衡的重要区域。 Synapse 63:881-894,2009年。2009年,Wiley-Liss,Inc.发布(匕首)

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